THE PHILADELPHIA CHROMOSOME

A Mutant Gene and the Quest to Cure Cancer at the Genetic Level

Science writer Wapner uses the development of a successful cure for a once-fatal form of leukemia to illustrate the application of genetic engineering to the frontiers of current medical practice.

The discovery of the structure of DNA unleashed the potential to use genetically engineered pharmaceuticals in the treatment of cancer. It took longer than the succeeding 10 years for phrases like “genetic mutation” and “chromosomal abnormality” to become part of the scientific vernacular. By 1959, when the available investigative tools were still primitive by today's standards, a researcher at the University of Pennsylvania discovered an abnormality in the relative sizes of two chromosomes. Ultimately, this led to an understanding of the role of oncogenes, but first a marriage had to take place. The prevailing theory, based on the study of chicken tumors, was that since cancers were contagious, they were caused by viral infection. After virologists determined the genetic makeup of viruses, they opened a second trajectory for the research. They made the remarkable discovery that a normal, proto-oncogenetic chicken gene was temporarily assimilated into an “infecting” virus where it mutated. Normally, the proto-oncogenes were also found in healthy humans, as well as chickens and other animals. Now that the gene was identified, a similar process was discovered in the Philadelphia Chromosome. In this case, a mutated oncogene was located at the point where two specific chromosomes split and interchanged positions before their parts were rejoined. The next problem was to establish the gene's role in normal cell regulation and how to block its functioning after it had mutated. Wapner weaves together the basic and applied science with the stories of the dedicated researchers, the broader supporting superstructure of modern medicine and the process of bringing pharmaceuticals to market.